In rhesus monkeys, caloric restriction (CR) delays the onset of sarcopenia, the age-related decline in skeletal muscle mass. Sarcopenia in monkeys parallels the phenotypes observed in people, and our published and preliminary data suggests that a deficiency in energy metabolism is central to muscle aging. It is unclear the extent to which reproductive hormone status influences the rate of muscle mass loss as a function of age. In humans, age is associated with increased fat storage and reduced muscle mass and function. Our work on sarcopenia suggests that these phenotypes may be linked. We hypothesize that gender differences in sarcopenia are linked to the impact of reproductive hormones on muscle energy metabolism and preservation of mass. To test this we will determine the cellular energetic signature induced by aging, CR, and gonadectomy, and relate intracellular phenotypes to whole tissue and whole animal measures. Aim 1: To determine gender and reproductive hormone effects in skeletal muscle energy metabolism and the dynamics of sarcopenia (1a) To determine gender differences in skeletal muscle energy metabolism with age and CR in banked vastus lateralis from ~23 year old Control and CR male and female monkeys (n=29) from our CR and aging longitudinal study using quantitative imaging, biochemical and lipidomic approaches. These intracellular measures will be analyzed against existing body composition data, skeletal muscle gene expression data, and TLC/GC serum lipid composition profiles. (1b) To determine the impact of reproductive hormone status on age-related muscle mass loss. Using existing data generated from Aim1a animals covering the ages ~17 to ~27 years (n=29), we will determine the (i) impact of aging and CR on reproductive hormones, (ii) impact of aging and reproductive hormone status on estimated muscle mass, and (iii) interaction between aging, CR, and reproductive hormone status on sarcopenia. Aim 2: To determine the impact of reproductive hormone suppression on muscle metabolism and composition. We will test the impact of surgical reproductive hormone suppression in males and females ~15 years of age (n=20 sham, n=20 suppressed). Muscle mass and composition, reproductive hormones, and intracellular metabolism will be assessed in vastus lateralis biopsies over a 36-month period. Serum measures of glucoregulatory function, adiponectin, and lipid composition will index perturbations in systemic metabolism. Our research team includes expertise in primate aging, endocrinology, and skeletal muscle metabolism, and is uniquely poised to conduct this work. We anticipate that this highly translational study will no only advance our understanding of skeletal muscle aging but will be relevant to a wider sphere, including the impact of reproductive hormone status on skeletal muscle and systemic metabolic regulation.